Division of Clinical Pharmacology and Toxicology, Geneva University Hospital, Geneva, Switzerland.
Research Center for Statistics, Geneva School of Economics and Management, University of Geneva, Geneva, Switzerland.
Res Synth Methods. 2017 Sep;8(3):312-320. doi: 10.1002/jrsm.1242. Epub 2017 Jun 5.
Clinical trials have different designs: In late stage drug development, the parallel trial design is the most frequent one; however, the crossover design is not rare; different techniques are used to analyse their results. Although both designs measure the same treatment effect, combining parallel and crossover trials in a meta-analysis is not straightforward. We present here a meta-analysis method based on generalised estimating equation (GEE) regression to combine aggregated results of crossover and parallel trials using a marginal estimation approach. This method is based on the fixed effects meta-analytic model; it allows combining average outcomes belonging to the exponential distributions obtained from trials of different designs and in particular from crossover trials with more than 2 periods and 2 treatments. By extending the methods proposed so far to combine the 2 trial designs, the GEE regression allows for adjusting for bias, such as a carry-over effect typical in crossover trials. In this paper, the GEE meta-analysis method is compared to the classical weighted average method with examples of published and simulated meta-analyses. Although the GEE can account for crossover specificities, it is limited by the availability of detailed trial information often encountered with reports of these trials.
在药物开发的后期，平行试验设计是最常见的；然而，交叉设计也不少见；不同的技术被用来分析它们的结果。虽然这两种设计都测量了相同的治疗效果，但在荟萃分析中合并平行和交叉试验并不简单。我们在这里提出了一种基于广义估计方程（GEE）回归的荟萃分析方法，通过边缘估计方法合并交叉和平行试验的汇总结果。这种方法基于固定效应荟萃分析模型；它允许合并来自不同设计的试验，特别是来自具有超过 2 个周期和 2 种治疗的交叉试验的指数分布的平均结果。通过将迄今为止提出的方法扩展到合并这两种试验设计，GEE 回归允许调整偏倚，例如交叉试验中典型的残留效应。在本文中，通过实例分析和模拟荟萃分析，将 GEE 荟萃分析方法与经典的加权平均方法进行了比较。虽然 GEE 可以考虑交叉设计的特殊性，但它受到详细试验信息的可用性的限制，而这些试验的报告通常存在这种限制。
